tbuckley/cabot-search huggingface dataset:
Pancreatitis and Hyperlipasemia in the Setting of Immune Checkpoint Inhibitor Therapy
Authors: Matthew J. Townsend, Mofei Liu, Anita Giobbie-Hurder, Jordan S. Sack, Nicole R. LeBoeuf, F. Stephen Hodi, Julia McNabb-Baltar, Shilpa Grover
Journal: Journal of the National Comprehensive Cancer Network (2023)

Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of pancreatic injury while receiving ICIs that is attributable to therapy remains unclear. We evaluated the etiology of hyperlipasemia in patients receiving ICIs, and the clinical characteristics, management, and outcomes of ICI-PI.We assessed 6,450 consecutive adult patients with cancer who received ICI doses between 2011 and 2019, 364 of whom had at least 1 instance of elevated serum lipase after ICI initiation and were included in our trial. Primary outcomes were the development of ICI-PI and ICI-induced acute pancreatitis (ICI-AP).Pancreatic injury was attributable to ICI use in 105 individuals (29% of those with hyperlipasemia; 1.6% overall). Of 27 patients with ICI-AP, 4 (15%) presented asymptomatically with hyperlipasemia and pancreatic inflammation on imaging. In multivariable regression, the presence of other immune-related adverse events was positively associated with ICI-AP (≥2 events: odds ratio, 5.43; 95% CI, 1.47-26.03). Compared with patients with other ICI-PI, those with ICI-AP more frequently required steroids (74% vs 4%), intravenous fluids (85% vs 10%), hospitalization (89% vs 9%), and permanent cessation of ICIs due to pancreatic injury (70% vs 3%), and less frequently continued therapy uninterrupted (0% vs 40%) (P<.01 for all). Of the 105 patients, 3 (3%) developed exocrine insufficiency and 9 (9%) developed endocrine insufficiency, which were concentrated among those with ICI-AP.A minority of occurrences of pancreatitis and hyperlipasemia in patients receiving ICIs are due to these therapies, supporting NCCN recommendations to exclude alternative etiologies. Because a notable proportion of patients with ICI-AP were asymptomatic but warranted treatment per current guidelines, abdominal imaging is diagnostically valuable in those with significant hyperlipasemia. Patients with ICI-AP should be monitored for exocrine pancreatic insufficiency. Many with hyperlipasemia who do not meet the criteria for AP can continue therapy uninterrupted.
NCCN Guidelines® Insights: Survivorship, Version 1.2023
Authors: Tara Sanft, Andrew Day, Shannon Ansbaugh, Saro Armenian, K. Scott Baker, Tara Ballinger, Wendy Demark-Wahnefried, Kristin Dickinson, Nathan Paul Fairman, Josephine Felciano, Tessa Faye Flores, Debra L. Friedman, Nicolette M. Gabel, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Divya Koura, Kimberly Lee, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Natalie Moryl, Heather Neuman, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Chirayu Patel, Lindsay Peterson, William Pirl, Andrea Porpiglia, M. Alma Rodriguez, Lidia Schapira, Anna L. Schwartz, Sophia Smith, Amye Tevaarwerk, Eric Yang, Phyllis Zee, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.
Protein Exaptation by Endogenous Retroviral Elements Shapes Tumor Cell Senescence and Downstream Immune Signaling
Authors: Reddick R. Walker, Katherine B. Chiappinelli
Journal: Cancer Research (2023)

Abstract Cancer cell senescence in lung squamous cell carcinoma (LUSC) is associated with a poor response to chemotherapies and immunotherapies due to promotion of an immunosuppressive tumor microenvironment. This environment is shaped by the senescence-associated secretory pathway, which recruits suppressive immune cell populations. In a recent study, Attig and colleagues identified a transcription factor–activated molecular switch that circumvents cellular senescence through increased expression of the calbindin protein. A human endogenous retrovirus (HERV) sequence upstream of the calbindin gene, CALB1, promotes the transcription of an HERVH-CALB1 transcript through a splice event at the third CALB1 exon in a process known as protein exaptation. The KLF5 transcription factor mediates this transcriptional activity by binding at the HERVH sequence, subsequently initiating the chimeric HERVH-CALB1 transcription. This increased expression of calbindin reduces CXCL8 chemokine production and downstream neutrophil recruitment in LUSC tumor cells. CALB1 exaptation by HERVH is one example by which endogenous retroelements (ERE) regulate immunity in human cancers, highlighting the emerging role of EREs in tumor immunity.
Affordable Cystic Fibrosis (CF) Transmembrane Conductance Regulator Modulator Drugs for CF: All CF Lives Worldwide Matter!
Authors: Marco Zampoli, Janine Verstraete, Cathy Baird, Greg Calligaro, Brenda Morrow
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Affordable CFTR Modulator Drugs for Cystic Fibrosis: All CF Lives Worldwide Matter!." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Proposed Principles for International Bioethics Conferencing: Anti-Discriminatory, Global, and Inclusive
Authors: Nancy S. Jecker, Vardit Ravitsky, Mohammad Ghaly, Jean-Christophe Bélisle-Pipon, Caesar Atuire
Journal: The American Journal of Bioethics (2023)

AbstractThis paper opens a critical conversation about the ethics of international bioethics conferencing and proposes principles that commit to being anti-discriminatory, global, and inclusive. We launch this conversation in the Section, Case Study, with a case example involving the International Association of Bioethics' (IAB's) selection of Qatar to host the 2024 World Congress of Bioethics. IAB's choice of Qatar sparked controversy. We believe it also may reveal deeper issues of Islamophobia in bioethics. The Section, Principles for International Bioethics Conferencing, sets forth and defends proposed principles for international bioethics conferencing. The Section, Applying Principles to Site Selection applies the proposed principles to the case example. The Section, Applying Principles Beyond Site Selection addresses other applications of the proposed principles. The Section, Objections responds to objections. We close (in the Section, Conclusion) by calling for a wider discussion of our proposed principles.One-Sentence Capsule Summary: How should bioethicists navigate the ethics of global bioethics conferencing?Keywords: Epistemic justiceglobal bioethicshuman rightsinternational bioethicsIslamophobiaRacism ACKNOWLEDGMENTSThe authors are grateful to Dorcas Kamuya for generous assistance and extensive contributions to the paper. The authors also wish to thank two anonymous reviewers for this journal and the journal's Editor for valuable comments that significantly improved the paper. All views expressed are solely the authors' own. They do not represent the International Association of Bioethics (IAB), its Board of Directors, or its membership; nor do they represent the Research Center for Islamic Legislation and Ethics (CILE), its faculty, or its associates.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Leisure-Time Physical Activity and Risk of Microvascular Complications in Individuals With Type 2 Diabetes: A UK Biobank Study
Authors: Frederik Pagh Bredahl Kristensen, Miguel Adriano Sanchez-Lastra, Knut Eirik Dalene, Borja del Pozo Cruz, Mathias Ried-Larsen, Reimar Wernich Thomsen, Ding Ding, Ulf Ekelund, Jakob Tarp
Journal: Diabetes Care (2023)

The aim of this study was to determine dose-response associations, including the minimal effective level, between leisure-time physical activity and risk of incident neuropathy, nephropathy, and retinopathy.This cohort study included 18,092 individuals with type 2 diabetes from the UK Biobank. Self-reported leisure-time physical activity was converted into MET-hours per week. Participants were categorized into no physical activity (0 MET-h/week), below recommendations (0-7.49 MET-h/week), at recommendations (7.5-14.9 MET-h/week), and above recommendations (≥15 MET-h/week). Microvascular complications were identified from hospital inpatient records using diagnosis codes. We used Cox proportional hazards regression analysis to calculate adjusted hazard ratios (aHRs) and restricted cubic splines to identify the minimal effective level of physical activity.During a median follow-up of 12.1 years, 672 individuals (3.7%) were diagnosed with neuropathy, 1,839 (10.2%) with nephropathy, and 2,099 (11.7%) with retinopathy. Any level of physical activity was associated with a lower risk of neuropathy and nephropathy but not retinopathy. Compared with those reporting no physical activity, the aHR of neuropathy was 0.71 (95% CI 0.53, 0.90) below recommendations, 0.73 (0.56, 0.96) at recommendations, and 0.67 (0.52, 0.87) above recommendations. Corresponding aHRs for nephropathy were 0.79 (0.68, 0.92), 0.80 (0.67, 0.95), and 0.80 (0.68, 0.95). The association with retinopathy was weaker, with aHRs of 0.91 (0.78, 1.06), 0.91 (0.77, 1.08), and 0.98 (0.84, 1.15), respectively.Any level of leisure-time physical activity was associated with a lower risk of neuropathy and nephropathy but not retinopathy in individuals with type 2 diabetes. For both neuropathy and nephropathy, the minimal effective physical activity level may correspond to <1.5 h of walking per week.
Contraception
Authors: Rachel Cannon, Kelly Treder, Elisabeth J. Woodhams
Journal: Annals of Internal Medicine (2023)

Contraception counseling and provision are vital components of comprehensive health care. An unplanned pregnancy can be particularly challenging for patients with chronic illness. Internal medicine physicians are uniquely positioned to assess pregnancy readiness and provide contraception, as they often intersect with pregnancy-capable patients at the moment of a new diagnosis or when providing ongoing care for a chronic medical condition. A shared decision-making counseling approach engages patients, ensures patient-centered care, and supports their choice of a contraceptive method that aligns with their reproductive plans and medical needs.
Response by Zeitler et al to Letter Regarding Article, “Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex”
Authors: Emily P. Zeitler, Stephen Kearing, Megan Coylewright, Devi Nair, Jonathan C. Hsu, Douglas Darden, A. James O’Malley, Andrea M. Russo, Sana M. Al-Khatib
Journal: Circulation (2023)
Long COVID-19 Cardiac Complications Are Associated With Autoimmunity to Cardiac Self-Antigens Sufficient to Cause Cardiac Dysfunction
Authors: Marco Cremonesi, Arianna Felicetta, Francesco Cannata, Simone Serio, Jasper J.P. van Beek, Sara Bombace, Ilaria My, Veronica Zanon, Chiara Catalano, Vasiliki Papadopoulou, Lorenzo Monti, Mauro Chiarito, Giulio Stefanini, Cristina Panico, Marco Francone, Enrico Lugli, Marinos Kallikourdis, Gianluigi Condorelli
Journal: Circulation (2023)

oronavirus disease 2019 (COVID-19) led to extensive morbidity and mortality.Attention is shifting to long-term effects persisting after acute infection, termed long/post-COVID-19, including cardiac sequelae. 1Cardiovascular magnetic resonance (CMR) abnormality is present at 6-month follow-up in half of patients recovered from COVID-19 with in-hospital high-sensitivity troponin elevation. 2Lack of preinfection data renders it hard to exclude causality from pre-existing conditions, rather than infection sequelae.Yet larger studies show increased risk of incident cardiovascular disease in the year after COVID-19, 3,4 suggesting that long/post-COVID-19 cardiac sequelae may become a major public health issue.Proposed mechanisms of COVID-19 cardiovascular involvement include direct damage by virus, or indirect, mediated by systemic inflammation/autoimmunity. 1 Autoimmunity to cardiac self-antigens could be triggered through "molecular mimicry" of antigens shared between COVID-19 and host cells, and/or through "bystander loss-of-tolerance, " where T or B cells, of random selfreactive specificity, are accidentally unleashed after receiving costimulation signals from the infection.The latter hypothesis could explain many features of acute and chronic COVID-19.First, T and B cell antigen speci
A biologic-device combination product delivering tumor-derived antigens elicits immunogenic cell death-associated immune responses against glioblastoma
Authors: Christopher Cultrara, Christopher Uhl, Kenneth Kirby, Essam Abed Elrazaq, Amelia Zellander, David W Andrews, Charles B Scott, Lorenzo Galluzzi, Mark A Exley, Jenny Zilberberg
Journal: Journal for ImmunoTherapy of Cancer (2023)

IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5-6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.Mouse (m) or human (h) variants of IGV-001 were prepared using GL261 mouse GBM cells or human GBM cells, respectively. BDCs containing vehicle or mIGV-001 were implanted in the flanks of C57BL/6 albino female mice in preventative and therapeutic experiments, optionally in combination with a programmed cell death 1 (PD-1) blocker. Bioactivity of the general approach was also measured against hepatocellular carcinoma Hepa 1-6 cells. Mice were followed for the growth of subsequently implanted or pre-existing tumors and survival. Draining lymph nodes from mice receiving mIGV-001 were immunophenotyped. mIGV-001 and hIGV-001 were analyzed for extracellular ATP and high mobility group box 1 (HMGB1) as indicators of immunogenic cell death (ICD), along with flow cytometric analysis of viability, surface calreticulin, and reactive oxygen species. Stress and cell death-related pathways were analyzed by immunoblotting.IGV-001 causes oxidative and endoplasmic reticulum stress in GL261 cells, resulting in a cytotoxic response that enables the release of antigenic material and immunostimulatory, ICD-associated molecules including ATP and HMGB1 from BDCs. Immunophenotyping confirmed that IGV-001 increases the percentage of dendritic cells, as well as effector, and effector memory T cells in BDC-draining lymph nodes. Consistent with these observations, preventative IGV-001 limited tumor progression and extended overall survival in mice intracranially challenged with GL261 cells, a benefit that was associated with an increase in tumor-specific T cells with effector features. Similar findings were obtained in the Hepa 1-6 model. Moreover, therapeutically administered IGV-001 combined with PD-1 delayed progression in GBM-bearing mice.These results support treatment with IGV-001 to induce clinically relevant ICD-driven anticancer immune responses in patients with GBM.
Comparative Effectiveness and Safety of Generic Versus Brand-Name Fluticasone–Salmeterol to Treat Chronic Obstructive Pulmonary Disease
Authors: William B. Feldman, Aaron S. Kesselheim, Jerry Avorn, Massimiliano Russo, Shirley V. Wang
Journal: Annals of Internal Medicine (2023)

Background: In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone–salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone–salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications. Objective: To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone–salmeterol among patients with COPD treated in routine care. Design: A 1:1 propensity score–matched cohort study. Setting: A large, longitudinal health care database. Patients: Adults older than 40 years with a diagnosis of COPD. Measurements: Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry. Results: Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]). Limitations: Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded. Conclusion: Use of generic and brand-name fluticasone–salmeterol was associated with similar outcomes among patients with COPD treated in routine practice. Primary Funding Source: National Heart, Lung, and Blood Institute.
Understanding Causes of Inferior Outcomes in Adolescents and Young Adults With Cancer
Authors: Julie A. Wolfson, Kelly M. Kenzik, Blake Foxworthy, John M. Salsman, Katherine Donahue, Marie Nelson, Mary Beth Littrell, Grant R. Williams, Jennifer M. Levine
Journal: Journal of the National Comprehensive Cancer Network (2023)

Individuals diagnosed with cancer as adolescents and young adults (AYAs; ages 15–39 years) face unique vulnerabilities. Compared with individuals diagnosed when younger (≤14 years) or older (≥40 years), AYAs have not seen the same improvement in survival. Furthermore, they sit at a complex moment of social, emotional, and cognitive development, and have a unique interface with the healthcare system. With these observations, NCI prioritized addressing the unique vulnerabilities among AYAs with cancer, and NCCN developed guidelines regarding optimal AYA cancer care. Improvements in certain locales have been seen in the wake of this focus on AYAs, suggesting that continuing to consider AYA outcomes in the context of their specific needs is critical as we strive toward additional improvements. However, it is key to consider the drivers of these outcomes to continue this trajectory. This review presents a holistic conceptual model that includes factors that influence outcomes among AYAs with cancer, including domains in these levels that influence both clinical outcomes (such as relapse and survival) and health-related quality of life (HRQoL). These include domains at the patient level, such as social constructs (race/ethnicity, socioeconomic status), behavior (adherence, risk-taking), biologic characteristics (cancer biology, host genetics), medical treatment (treatment regimen, risk-based survivorship care), and treatment-related toxicities. The model also includes domains at the system level, which include treatment location (NCI designation, facility model, AYA program presence), clinical trial enrollment, transdisciplinary communication, fertility preservation, and psychosocial support. Recognizing these multiple factors at the level of the individual and the healthcare system influence AYA outcomes (from HRQoL to survival), it is key not only to consider patient-level interventions and development of novel cancer agents but also to develop systems-level interventions that can be executed in parallel. In this way, the impact can be expanded to a vast number of AYAs.
Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events
Authors: Bertram Pitt, Deepak L. Bhatt, Michael Szarek, Christopher P. Cannon, Lawrence A. Leiter, Darren K. McGuire, Julia B. Lewis, Matthew C. Riddle, Adriaan A. Voors, Marco Metra, Lars H. Lund, Michel Komajda, Jeffrey M. Testani, Christopher S. Wilcox, Piotr Ponikowski, Renato D. Lopes, Justin A. Ezekowitz, Franklin Sun, Michael J. Davies, Subodh Verma, Mikhail N. Kosiborod, Ph. Gabriel Steg
Journal: JACC Heart Failure (2023)

Approximately 25% of patients admitted to hospitals for worsening heart failure (WHF) are readmitted within 30 days.The authors conducted a post hoc analysis of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-WHF) trial to evaluate the efficacy of sotagliflozin versus placebo to decrease mortality and HF-related events among patients who began study treatment on or before discharge from their index hospitalization.The main endpoint of interest was cardiovascular death or HF-related event (HF hospitalization or urgent care visit) occurring within 90 and 30 days after discharge for the index WHF hospitalization. Treatment comparisons were by proportional hazards models, generating HRs, 95% CIs, and P values.Of 1,222 randomized patients, 596 received study drug on or before their date of discharge. Sotagliflozin reduced the main endpoint at 90 days after discharge (HR: 0.54 [95% CI: 0.35-0.82]; P = 0.004) and at 30 days (HR: 0.49 [95% CI: 0.27-0.91]; P = 0.023) and all-cause mortality at 90 days (HR: 0.39 [95% CI: 0.17-0.88]; P = 0.024). In subgroup analyses, sotagliflozin reduced the 90-day main endpoint regardless of sex, age, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, or mineralocorticoid receptor agonist use. Sotagliflozin was well-tolerated but with slightly higher rates of diarrhea and volume-related events than placebo.Starting sotagliflozin before discharge in patients with type 2 diabetes hospitalized for WHF significantly decreased cardiovascular deaths and HF events through 30 and 90 days after discharge, emphasizing the importance of beginning sodium glucose cotransporter treatment before discharge.
Pulmonary Artery Hypoplasia in Neonates With Tetralogy of Fallot
Authors: Christopher J. Petit, Andrew C. Glatz, Andrew B. Goldstone, Mark A. Law, Jennifer C. Romano, Shiraz A. Maskatia, Paul J. Chai, Jeffrey D. Zampi, Jeffery J. Meadows, George T. Nicholson, Shabana Shahanavaz, Athar M. Qureshi, Courtney E. McCracken, Christopher E. Mascio, Sarosh P. Batlivala, Ivor B. Asztalos, Steven J. Healan, Justin D. Smith, Joelle A. Pettus, Asaad Beshish, James E.B. Raulston, Krissie M. Hock, Amy L. Pajk, Bryan H. Goldstein
Journal: Journal of the American College of Cardiology (2023)